Binding affinities of the SH2 domains of ZAP-70, p56/ck and Shc to the chain ITAMs of the T-cell receptor determined by surface plasmon resonance

Autor: Richard H. Ingraham, Josephine Schembri-King, Scott Jakes, Maurice M. Morelock, Mark E. Labadia
Rok vydání: 1996
Předmět:
Zdroj: Journal of Leukocyte Biology. 59:740-746
ISSN: 1938-3673
0741-5400
Popis: The chains of the T cell receptor complex play a critical role in the initiation of proximal signaling events upon T cell activation. Three pairs of potential tyrosine phosphorylation sites are located within the cytoplasmic domains of the chains. Subsequent to engagement of the T cell receptor, one or more of these tyrosine residues is phosphorylated. The phosphotyrosine residues, along with flanking amino acids, form an activation motif (and are shared by signaling subunits in the TCR, B cell receptor, and FcγRI) termed tyrosine-based activation motifs (ITAMs). ITAMs serve as binding sites for SH2 domain-containing proteins. Recent evidence suggests that the chains provide docking space for several key signal transduction molecules such as ZAP-70, p56 lck, and Shc. To determine if ZAP-70, p56 lck, and Shc bind to particular chain ITAM sequences, quantitative free-solution measurements of binding affinities (Kd) were obtained by use of surface plasmon resonance technology. The results indicate that binding affinities of distinct SH2 domains to individual and paired phosphorylation sites greatly differ, and may dictate the sequence of signal transduction events.
Databáze: OpenAIRE
Externí odkaz: